Maternal Dietary Intake of Vitamin A and Risk of Orofacial Clefts: A Population-Based Case-Control Study in Norway

Abstract

Orofacial clefts—among the commonest birth defects worldwide—are relatively frequent in Norway. At the same time, adult Norwegians have a comparatively high intake of vitamin A in diet and supplements. This Norwegian population-based case-control study, covering the years 1996–2001, was an attempt to assess the association, if any, between maternal vitamin A intake from both diet and supplements and the risk of having a newborn infant with an orofacial cleft. Adequate data were available for 535 cases: 188 with cleft palate only and 347 with cleft lip (with or without cleft palate). Control subjects numbered 693. Dietary vitamin A was estimated using “retinol equivalents” calculated as dietary retinol plus one-twelfth of the estimated beta-carotene intake. The offspring of women in the highest quartile of total maternal vitamin A intake had an adjusted odds ratio (OR) for an isolated cleft palate alone of 0.47 (95% confidence interval [CI], 0.24–0.94), compared to the offspring of women with the lowest intake. There was, however, no statistically significant association between total vitamin A intake and isolated cleft lip, with or without cleft palate. The children of women whose vitamin A intake was above the 95th percentile had a lower estimated risk of all isolated clefts (adjusted OR, 0.48; 95% CI, 0.20–1.14) than those whose mother's vitamin A intake was at the 40th–60th percentile. Comparing a high with a median intake of retinol and beta-carotene separately, the adjusted ORs of all isolated clefts were, respectively, 0.4 (95% CI, 0.15–1.02) and 0.41 (95% CI, 0.17–0.97). These findings indicate that a high maternal vitamin A intake protects against isolated cleft palate. The evidence for protection against cleft lip, with or without cleft palate, is much less persuasive. The investigators conclude that maternal consumption of foods high in vitamin A during early pregnancy should not be discouraged.